The Ets family of genes have been shown to be important regulators of hemato-poietic genes by functioning as transcription factors. Their dysregulated expression may lead to malignant transformation. Studies are being conducted to understand the function and regulatory controls of these genes during mouse development. Analyses are being conducted to determine the normal pattern of expression of these genes during embryogenesis and later stages of life. Although these genes appear to be evolutionarily highly related, the mechanisms governing their very different, tissue-specific and developmental pattern of expression is not understood. Experiments are being performed to identify the major cis- acting transcriptional regulatory elements of these genes through specially-designed constructs introduced into transgenic mice. Identification of the control elements will enable new strategies for manipulating the expression of these genes and, ultimately, other genes which are dependent upon Ets transcriptional activation. Further understanding regarding the function of the Ets genes is being addressed through the overexpression of the Ets genes in various tissues during development in transgenic mice. In addition, the importance of Ets expression will be clarified through the completion of ongoing experiments to produce targeted null mutations of the Ets genes using homologous recombination in embryonic stem cells and transgenic mice.